Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States

Prepregnancy Counseling and Care for Persons of Childbearing Age with HIV

Overview

The Centers for Disease Control and Prevention (CDC), the American College of Obstetricians and Gynecologists (ACOG), and other national organizations recommend offering all persons of childbearing potential comprehensive family planning and the opportunity to receive prepregnancy counseling and care as a component of routine primary medical care. The purpose of prepregnancy care is to improve the health of each person before conception by identifying risk factors for adverse outcomes for the pregnant person and their fetus, tailoring education and counseling to individual needs, and treating or stabilizing medical conditions to optimize outcomes for the pregnancy and the fetus/newborn.^1,2 Prepregnancy care is not something that occurs in a single clinical visit; rather, it requires integrating ongoing care and interventions into primary care to address people’s needs during the different stages of reproductive life. Integrating comprehensive family planning and prepregnancy care into routine health care visits can help people with HIV reach their desired reproductive outcomes by supporting them to make informed decisions about their fertility and contraceptive use that are aligned with their preferences and reproductive goals.^3–6 Providers should initiate and document a nonjudgmental conversation with all persons of reproductive age about their reproductive desires because they may be reluctant to bring up the subject themselves.^7–11 A meta-analysis of 50 studies found a 42% prevalence of fertility desire among persons with HIV. In a pooled analyses, fertility desire was associated with being on antiretroviral therapy (ART), male sex, age younger than 30, being married/cohabitating, a secondary education or higher, and being childless.¹² Health care providers who routinely care for persons of reproductive age with HIV play an important role in promoting prepregnancy health and informed reproductive decisions. Pregnancy intentions may not be binary and may change over time, thus underscoring the need for health care providers to engage in ongoing discussions to support dynamic pregnancy intentions.¹¹ However, even among providers who offer primary care to persons with HIV, the delivery of comprehensive reproductive counseling often falls short of the current guidelines.^13–15

The fundamental principles of prepregnancy counseling and care are outlined in the CDC Preconception Care Work Group’s Recommendations to Improve Preconception Health and Health Care. In addition to the general components of prepregnancy counseling and care that are appropriate for all persons of reproductive age, persons with HIV have specific needs that should be addressed.^16–19

• Discuss reproductive options; actively assess their pregnancy intentions on an ongoing basis throughout the course of care; and, when appropriate, make referrals to HIV and reproductive health specialists, including experts in reproductive endocrinology and infertility when necessary. The HIV status of one or both parents should not be a reason to withhold standard of care infertility treatment and assist individuals and couples in reaching their desired reproductive outcomes.
• Encourage individuals to disclose their HIV status to their partner or co-parent before pregnancy if it is safe to do so. However, this disclosure should not be a requirement of assisting couples in achieving pregnancy.
• Recognize that the primary treatment goal for persons with HIV who are planning a pregnancy should include sustained suppression of plasma viral load below the limit of detection before conception for their own health, to minimize the risk of perinatal HIV transmission, and to prevent sexual HIV transmission to a partner without HIV (see Reproductive Options for Couples When One or Both Partners Have HIV). Inform individuals considering or planning pregnancy that with ART starting before pregnancy and maintained throughout pregnancy and with undetectable viral load at delivery, there is no risk of HIV transmission to the infant.^20,21
• Explain that persons with HIV who take ART as prescribed and who achieve and maintain an undetectable viral load will not transmit HIV through sex, commonly known as Undetectable = Untransmittable or U=U. For more information, see Let’s Stop HIV Together.
• Encourage sexual partners to receive HIV counseling and testing so that they can seek HIV care if they have HIV or seek advice about HIV prevention, including pre-exposure prophylaxis (PrEP), if they do not have HIV (see Pre-exposure Prophylaxis (PrEP) to Reduce the Risk of Acquiring HIV During Periconception, Antepartum, and Postpartum Periods).
• Ask about the use of alcohol, tobacco, and other substance. Provide or refer to evidence-based interventions for substance use disorder, including medication-assisted treatment for opiate use disorder (e.g., methadone, buprenorphine), and counsel patients on how to manage health risks (e.g., access to a syringe services program). Frazier et al.²² reported that overall, 39% of women with HIV of reproductive age reported current drinking and 10% reported binge drinking. Compared to non-drinkers, binge drinkers were less likely to adhere to ART or be virally suppressed and more likely to smoke and use drugs. Between 2007 and 2019, marijuana use during pregnancy among women with HIV increased from 7.1% to 11.7%, whereas alcohol and opioid use were unchanged. Postpartum alcohol (44.4%), marijuana (13.6%), and concomitant alcohol and marijuana (10%) use were common; marijuana use increased from 10.2% in 2006 to 23.7% in 2019, whereas postpartum alcohol use was unchanged.²
• Ask pregnant people whether they feel safe at home and offer assistance or referrals for those experiencing intimate partner violence (IPV) or requesting it.
• Counsel on maintaining a healthy diet and healthy weight before and during pregnancy.
• Counsel people who are contemplating pregnancy to take a daily multivitamin that contains 400 mcg of folic acid to help prevent neural tube defects (NTDs). Individuals with a history of having a child with NTDs, a family history of NTDs, or on certain anti-epileptic medications, especially valproic acid, are candidates for receiving a higher dose (1,000–4,000 mcg) of folic acid. Higher doses of folate may also be considered for persons receiving trimethoprim/sulfamethoxazole (TMP/SMX) who are trying to conceive (see Special Considerations in Pregnancy in Pneumocystis Pneumonia).
• Educate and counsel about the risk factors for perinatal HIV transmission, the strategies to reduce those risks, and the potential effects of HIV or taking antiretroviral (ARV) drugs during pregnancy on pregnancy course and outcomes.
• Provide patient-centered, evidence-based counseling to support shared decision-making about infant feeding (see Infant Feeding for Individuals with HIV in the United States). Information about and plans for infant feeding should be reviewed throughout pregnancy and again after delivery
• Support shared decision-making about ART. Educate and counsel on the factors that affect the selection of ARVs for persons who are trying to conceive, are pregnant, or postpartum. For more information, see Teratogenicity, updated guidance about the use of dolutegravir in pregnancy in Recommendations for Use of Antiretroviral Drugs During Pregnancy, Dolutegravir, and Appendix C: Antiretroviral Counseling Guide for Health Care Providers.
• Consider the following factors when prescribing ART to persons of childbearing potential: the regimen’s effectiveness, an individual’s hepatitis B virus (HBV) status, the possible adverse outcomes for the pregnant person and their fetus, the likelihood of developing drug resistance, and the possible adverse outcomes for the mother and fetus.^24–26
• Use the prepregnancy period to modify the ARV regimen for persons who are contemplating pregnancy to optimize virologic suppression and minimize potential adverse effects (see Recommendations for Use of Antiretroviral Drugs During Pregnancy and Table 5). Recognize that individuals with perinatally-acquired HIV may have special needs (e.g., psychosocial support, adherence support)²⁷ (see Prenatal Care, Antiretroviral Therapy, and HIV Management in People with Perinatal-Acquired HIV Infection).
• Recognize that transgender and gender-diverse people who were assigned female sex at birth may have special needs.²⁸. For transgender men attempting pregnancy, the use of testosterone may induce hypothalamic-pituitary-gonadal suppression leading to decreased ovulation.²⁹
• Evaluate and manage therapy-associated adverse effects (e.g., hyperglycemia, anemia, hepatotoxicity) that may affect maternal-fetal health outcomes.
• Administer all vaccines as indicated (see Guidance for Vaccine Recommendations for Pregnant and Breastfeeding Women and 2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host), which includes vaccination for influenza, pneumococcus, HBV, tetanus, and SARS-CoV-2. All persons, including those with HIV, should receive Tdap (tetanus, diphtheria, and pertussis) vaccination during pregnancy.
• Offer all persons who currently do not desire pregnancy a full range of contraceptive methods to help them achieve their fertility goals. Persons with HIV can use all available contraceptive methods, including hormonal contraception (e.g., pill, patch, ring, injection, implant) and intrauterine devices (IUDs).³⁰ Providers should be aware of the presence of other medical co-morbidities and potential interactions between ARV drugs, hormonal contraceptives, and other medications that could lower contraceptive efficacy or increase the risk of such adverse effects as blood clots (see Table 3 below).
• Offer emergency contraception as appropriate, including emergency contraceptive pills and IUD (see the ACOG Practice Bulletin on Emergency Contraception). Emergency contraceptive pills that contain estrogen and progestin and those that only contain levonorgestrel (LNG) may have interactions with ARV drugs that are similar to the ones observed with combined oral contraceptives.³¹ ACTG 5375 showed that doubling the dose of LNG from 1.5 mg to 3 mg successfully increased LNG exposure in women receiving efavirenz (EFV)-based ART.³² No data are available on potential interactions between ARV drugs and ulipristal acetate, a progesterone receptor modulator; however, ulipristal acetate is metabolized predominantly by cytochrome P450 (CYP) 3A4, so interactions may occur (see the HIV Drug Interaction Checker).
• Optimize the health of people with HIV prior to pregnancy (e.g., ensure appropriate folate intake, test for all sexually transmitted infections and treat as indicated, consider the teratogenic potential of all prescribed medications, and consider switching to safer medications).

Drug–Drug Interactions Between Hormonal Contraceptives and Antiretroviral Therapy

Data on drug interactions between ARVs and hormonal contraceptives primarily come from drug labels and several studies on the pharmacokinetics (PKs) and pharmacodynamics among the different forms of contraception and ARVs.^31,33–54 The contraceptive effectiveness of the levonorgestrel IUD is largely through local (i.e., intrauterine) release of levonorgestrel, not through systemic absorption. CDC’s U.S. Medical Eligibility Criteria for Contraceptive Use lists the levonorgestrel IUD as category 1 (no restrictions) in drug interactions with all ARVs in women who already have an IUD and category 1/2 (benefits outweigh risk) for those initiating the use of an IUD.

Hormonal contraceptives can be used with ARVs in persons with HIV without other contraindications. An alternative or additional contraceptive method may be recommended when drug interactions are known. For persons receiving darunavir/ritonavir (DRV/r)-based ART, an alternative or additional contraception may be considered because the area under the curve (AUC) for oral contraceptive hormones may be decreased.⁵⁵ Cobicistat-boosted protease inhibitors (PIs) are contraindicated with drosperinone-containing hormonal contraceptives due to the potential for hyperkalemia.⁵¹ Depot medroxyprogesterone acetate (DMPA) can be used without restriction because of its relatively higher dose than other progesterone-based contraception, and limited studies have shown no significant interaction between DMPA and ARVs.^34,36,46,56

Several studies have shown that the use of EFV decreases the effectiveness of hormonal implants and hormonal vaginal rings. Although contraceptive implants (e.g., etonogestrel [ENG], LNG) generally can be used in people who are receiving ARVs, both PK and clinical data suggest that these implants have decreased efficacy when used with EFV-based regimens.^44,57–59 Scarsi et al. reported that the geometric mean ratios of LNG concentrations (patients taking EFV-based ART vs. ART-naive patients) were 0.53 at 24 weeks and 0.43 at 48 weeks. Three pregnancies occurred in the EFV group (15%) between Week 36 and Week 48, whereas no pregnancies occurred in the ART-naive or nevirapine (NVP) groups.⁴⁸

In a study of 570 women with HIV in Eswatini, formerly known as Swaziland, who had LNG implants (i.e., Jadelle), none of the women on NVP- or lopinavir/ritonavir-based regimens (n = 208 and n = 13, respectively) became pregnant, whereas 15 women on EFV (n = 121; 12.4%) became pregnant.⁴⁴ A prospective study in seven African countries collected data from 5,153 women with HIV who were followed for 1 to 3 years. During the follow-up period, 40% used injectables, 14% used oral contraceptives, and 9% of the women used implants (mostly LNG, which is not available in the United States, where ENG is approved); 31% of these women took ART during the follow-up period, mostly NVP-containing (75%) or EFV-containing (15%) regimens. Among women who were not using contraception, pregnancy rates were 13.2 per 100 person-years for those who were on ART and 22.5 per 100 person-years for those who were not on ART. Implants greatly reduced the incidence of pregnancy among women on ART (adjusted hazard ratio [aHR] 0.06; 95% confidence interval [CI], 0.01–0.45) and women who were not on ART (aHR 0.05; 95% CI, 0.02–0.11). Injectables and oral contraceptives also reduced pregnancy risk but to lesser degrees. A potential lesser degree of effectiveness of these methods may be due to their greater dependence on user action, as compared to longer acting methods. ART use did not significantly diminish contraceptive effectiveness, although all methods showed non-significant reduced contraceptive effectiveness when people used EFV concurrently.⁶⁰

In a retrospective study among 1,152 women with HIV using either EFV or NVP and ENG or LNG implants, 115 pregnancies occurred, yielding a pregnancy incidence rate of 6.32 (5.27–7.59), with a rate of 9.26 among ENG and 4.74 among LNG implant users, respectively. Pregnancy incidence rates did not differ between EFV- and NVP-based regimens (incidence rate ratio [IRR] = 1.00; 95% CI, 0.71–1.43). No pregnancies were recorded among women on PI-based regimens. Pregnancy rates of EFV- and NVP-containing regimens were similar at 6.41 (4.70–8.73) and 6.44 (5.13–8.07), respectively. Pregnancy rates differed by implant type with LNG implant users half as likely to become pregnant as ENG implant users (IRR = 0.51; 95% CI, 0.33–0.73, P > 0.01).⁶¹ A study of 42 women in Malawi (30 women with HIV on EFV and LNG, and 12 women without HIV on LNG) showed that EFV users had lower LNG concentrations that non EFV users, and one-third of the EFV/LNG users had LNG concentrations <180 pg/mL, which is the suggested minimum level for efficacy. No pregnancies were reported over 60 women-years of follow-up.⁶²

Genetic contributions also may influence observed drug–drug interactions between contraceptives and ARVs. In a study of 19 women not on ART (control group), 19 women on EFV, and 19 women on NVP all received ENG implants. Women in the EFV group with CYP 2B6 516 G>T had 43% lower ENG minimum plasma concentration (C_min) and 34% lower AUC from 0 to 24 h (AUC_0–24) at 24 weeks. For women on NVP, those with NR1I2 63396 C>T had lower ENG C_min and 37% lower AUC_0–24 at 24 weeks.⁵² Haas et al. reported that EFV reduced the median ENG level by at least 93% in CYP2B6 slow metabolizers versus by 75% in normal and intermediate metabolizers. EFV reduced median ethinyl estradiol concentration by 75% in slow metabolizers and 41% in normal and intermediate metabolizers among women using hormonal vaginal ring contraceptive⁶³.

Other medications, such as those for tuberculosis (TB) treatment and ARVs, also may have drug–drug interactions with contraceptives. A PK study of DMPA among women with HIV/TB coinfection who received EFV-based treatment and rifampicin-based TB treatment showed that among 42 evaluable women, five women (11.9%; 95% CI, 4.0–25.6%) had medroxyprogesterone acetate (MPA) <0.1 ng/mL at Week 12, the level above which ovulation is prevented; of these women, one had MPA <0.1 ng/mL at Week 10. The median clearance of MPA was higher in women on EFV compared with women with HIV who were not on ART, thus leading to subtherapeutic concentrations of MPA in 12% of women at Week 12.⁶⁴ The authors suggest redosing DMPA more frequently,⁶⁵ such as every 8 to 10 weeks. Haas et al. studied the interaction between DMPA, EFV, rifampicin, and isoniazid (INH) during treatment for HIV and tuberculosis. There were no associations between either CYP2B6 or N-acetyltransferase 2 (NAT2) genotype and MPA C_min at Week 12. The study was not designed to distinguish inductive effects of rifampicin from possible inhibitory effects of isoniazid on MPA clearance. Nevertheless, the authors recommended that more frequent DMPA dosing may be appropriate for women receiving all these medications.⁶⁶

Because data are limited on pregnancy rates among persons on different hormonal contraceptives and ARVs, some of the dosing recommendations in Table 3 are based on consensus expert opinion. Whenever possible, the recommendations are based on available data regarding PK interactions between ARVs and combined hormonal methods, DMPA, and LNG and ENG implants. The smallest decrease in PK for which an alternative method was recommended was a 14% decrease in norethindrone (with DRV/r). The Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission (the Panel) does not recommend any change in ethinyl estradiol dose in people who are receiving etravirine (ethinyl estradiol increased 22%) or rilpivirine (ethinyl estradiol increased 14%). In a secondary analysis of 85 cisgender women enrolled in HPTN 077, compared to women reporting no hormonal contraception (n = 6), oral contraceptive use (n =18) was associated with lower cabotegravir-long acting (CAB-LA) peak concentration but was not associated with other PK parameters, suggesting this association is not likely to be clinically significant. No other hormonal contraceptive type (injectable, implants, and other) was associated with significant differences in CAB-LA PK parameters.⁶⁷

Another contraceptive vaginal ring containing segesterone/ethinyl estradiol (Annovera) has recently been approved by the U.S. Food and Drug Administration. No available drug–drug interaction studies with this contraceptive vaginal ring and ARV and CYP inducers/inhibitors are known. The contraceptive may possibly be metabolized in the same way as ENG and ethinyl estradiol in the NuvaRing. Our recommendation is extrapolated from what is known with the etonogestrel/ethinyl estradiol (NuvaRing) vaginal ring.⁵⁴

Table 3. Drug Interactions Between Antiretroviral Agents and Hormonal Contraceptives

Note: All recommendations in this table are based on consensus expert opinion. Additional information can be found in CDC’s Update to U.S. Medical Eligibility Criteria for Contraceptive Use, 2016: Updated Recommendations for the Use of Contraception Among Women at High Risk for HIV Infection.⁶⁸

References

1. American College of Obstetricians and Gynecologists. ACOG committee opinion no. 762: prepregnancy counseling. Obstet Gynecol. 2019;133(1):e78-e89. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30575679.
2. Elwood C, Kennedy VL, Loutfy M, Poliquin V, Boucoiran I, Yudin MH. The Canadian HIV pregnancy planning guidelines: what pregnancy care providers need to know about HIV transmission and pre-conception considerations. J Obstet Gynaecol Can. 2021;43(7):884-887. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33272875.
3. Salters K, Loutfy M, de Pokomandy A, et al. Pregnancy incidence and intention after HIV diagnosis among women living with HIV in Canada. PLoS One. 2017;12(7):e0180524. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28727731.
4. Aebi-Popp K, Mercanti V, Voide C, et al. Neglect of attention to reproductive health in women with HIV infection: contraceptive use and unintended pregnancies in the Swiss HIV Cohort Study. HIV Med. 2018;19(5):339-346. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29336516.
5. Sutton MY, Zhou W, Frazier EL. Unplanned pregnancies and contraceptive use among HIV-positive women in care. PLoS One. 2018;13(5):e0197216. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29771940.
6. Dude AM, Miller ES, Garcia PM, Yee LM. Unintended pregnancy and viral suppression in pregnant women living with HIV. Am J Obstet Gynecol MFM. 2021;3(2):100300. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33359637.
7. Rahangdale L, Stewart A, Stewart RD, et al. Pregnancy intentions among women living with HIV in the United States. J Acquir Immune Defic Syndr. 2014;65(3):306-311. Available at: http://www.ncbi.nlm.nih.gov/pubmed/24525467.
8. Matthews LT, Beyeza-Kashesya J, Cooke I, et al. Consensus statement: supporting safer conception and pregnancy for men and women living with and affected by HIV. AIDS Behav. 2018;22(6):1713-1724. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28501964.
9. Cohn SE, Haddad LB, Sheth AN, et al. Parenting desires among individuals living with human immunodeficiency virus in the United States. Open Forum Infect Dis. 2018;5(10):ofy232. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30302356.
10. Skerritt L, de Pokomandy A, O’Brien N, et al. Discussing reproductive goals with healthcare providers among women living with HIV in Canada: the role of provider gender and patient comfort. Sex Reprod Health Matters. 2021;29(1):1932702. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34165395.
11. Skerritt L, Kaida A, O’Brien N, et al. Patterns of changing pregnancy intentions among women living with HIV in Canada. BMC Womens Health. 2021;21(1):350. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34615492.
12. Yan X, Du J, Ji G. Prevalence and factors associated with fertility desire among people living with HIV: a systematic review and meta-analysis. PLoS One. 2021;16(3):e0248872. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33735265.
13. Gokhale RH, Bradley H, Weiser J. Reproductive health counseling delivered to women living with HIV in the United States. AIDS Care. 2017;29(7):928-935. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28114813.
14. Tanner AE, Chambers BD, Philbin MM, et al. The intersection between women’s reproductive desires and HIV care providers’ reproductive health practices: a mixed methods analysis. Matern Child Health J. 2018;22(9):1233-1239. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30008042.
15. Teodoro N, Fu A, Ohly NT, Shalev N, Matseoane-Peterssen D, Westhoff CL. Long-acting reversible contraception knowledge, attitudes and use among HIV-infected and -uninfected women and their providers. Contraception. 2019;100(4):269-274. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31226320.
16. Lampe MA. Human immunodeficiency virus-1 and preconception care. Matern Child Health J. 2006;10(5 Suppl):S193-195. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16832609.
17. Aaron EZ, Criniti SM. Preconception health care for HIV-infected women. Top HIV Med. 2007;15(4):137-141. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17721000.
18. Anderson J. Women and HIV: motherhood and more. Curr Opin Infect Dis. 2012;25(1):58-65. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22156896.
19. Jones D, Chakhtoura N, Cook R. Reproductive and maternal healthcare needs of HIV infected women. Curr HIV/AIDS Rep. 2013;10(4):333-341. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23918674.
20. Mandelbrot L, Tubiana R, Le Chenadec J, et al. No perinatal HIV-1 transmission from women with effective antiretroviral therapy starting before conception. Clin Infect Dis. 2015;61(11):1715-1725. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26197844.
21. Sibiude et al. Zero vertical transmissions from over 5,000 pregnant women with undetectable HIV in France. Presented at: Conference on Retroviruses and Opportunistic Infections; 2022. Virtual. Available at: https://www.eatg.org/hiv-news/croi-2022-zero-vertical-transmissions-from-over-5000-pregnant-women-with-undetectable-hiv-in-france.
22. Frazier EL, Esser MB, McKnight-Eily LR, Zhou W, Chavez PR. Alcohol use among HIV-positive women of childbearing age, United States, 2013–2014. AIDS Care. 2021;33(8):1024-1036. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32808534.
23. Yee LM, Kacanek D, Brightwell C, et al. Marijuana, opioid, and alcohol use among pregnant and postpartum individuals living with HIV in the U.S. JAMA Netw Open. 2021;4(12):e2137162. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34860242.
24. Cotter AM, Garcia AG, Duthely ML, Luke B, O’Sullivan MJ. Is antiretroviral therapy during pregnancy associated with an increased risk of preterm delivery, low birth weight, or stillbirth? J Infect Dis. 2006;193(9):1195-1201. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16586354.
25. Tuomala RE, Shapiro DE, Mofenson LM, et al. Antiretroviral therapy during pregnancy and the risk of an adverse outcome. N Engl J Med. 2002;346(24):1863-1870. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12063370.
26. Stek AM. Antiretroviral medications during pregnancy for therapy or prophylaxis. Curr HIV/AIDS Rep. 2009;6(2):68-76. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19358777.
27. Byrne L, Sconza R, Foster C, Tookey PA, Cortina-Borja M, Thorne C. Pregnancy incidence and outcomes in women with perinatal HIV infection. AIDS. 2017;31(12):1745-1754. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28590327.
28. American College of Obstetricians Gynecologists’ Committee on Gynecologic Practice, American College of Obstetricians Gynecologists’ Committee on Health Care for Underserved Women. Health care for transgender and gender diverse individuals: ACOG Committee Opinion, number 823. Obstet Gynecol. 2021;137(3):e75-e88. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33595253.
29. Taub RL, Ellis SA, Neal-Perry G, Magaret AS, Prager SW, Micks EA. The effect of testosterone on ovulatory function in transmasculine individuals. Am J Obstet Gynecol. 2020;223(2):229 e221-229 e228. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32044312.
30. Centers for Disease C, Prevention. Update to CDC’s U.S. medical eligibility criteria for contraceptive use, 2010: revised recommendations for the use of hormonal contraception among women at high risk for HIV infection or infected with HIV. MMWR Morb Mortal Wkly Rep. 2012;61(24):449-452. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22717514.
31. Carten ML, Kiser JJ, Kwara A, Mawhinney S, Cu-Uvin S. Pharmacokinetic interactions between the hormonal emergency contraception, levonorgestrel (Plan B), and efavirenz. Infect Dis Obstet Gynecol. 2012;2012:137192. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22536010.
32. Scarsi KK, Smeaton LM, Podany AT, et al. PK of dose-adjested emergency contraception with EFV-based ART in ACTH 5375. Presented at: Conference on Retroviruses and Opportunistic Infections; 2021. Virtual Conference.
33. Vogler MA, Patterson K, Kamemoto L, et al. Contraceptive efficacy of oral and transdermal hormones when co-administered with protease inhibitors in HIV-1-infected women: pharmacokinetic results of ACTG trial A5188. J Acquir Immune Defic Syndr. 2010;55(4):473-482. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20842042.
34. Cohn SE, Park JG, Watts DH, et al. Depo-medroxyprogesterone in women on antiretroviral therapy: effective contraception and lack of clinically significant interactions. Clin Pharmacol Ther. 2007;81(2):222-227. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17192768.
35. Hoyt MJ, Storm DS, Aaron E, Anderson J. Preconception and contraceptive care for women living with HIV. Infect Dis Obstet Gynecol. 2012;2012:604183. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23097595.
36. Nanda K, Amaral E, Hays M, Viscola MA, Mehta N, Bahamondes L. Pharmacokinetic interactions between depot medroxyprogesterone acetate and combination antiretroviral therapy. Fertil Steril. 2008;90(4):965-971. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17880953.
37. Sevinsky H, Eley T, Persson A, et al. The effect of efavirenz on the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and norgestimate in healthy HIV-negative women. Antivir Ther. 2011;16(2):149-156. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21447863.
38. Robinson JA, Jamshidi R, Burke AE. Contraception for the HIV-positive woman: a review of interactions between hormonal contraception and antiretroviral therapy. Infect Dis Obstet Gynecol. 2012;2012:890160. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22927715.
39. Tseng A, Hills-Nieminen C. Drug interactions between antiretrovirals and hormonal contraceptives. Expert Opin Drug Metab Toxicol. 2013;9(5):559-572. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23425052.
40. Landolt NK, Phanuphak N, Ubolyam S, et al. Efavirenz, in contrast to nevirapine, is associated with unfavorable progesterone and antiretroviral levels when co-administered with combined oral contraceptives. J Acquir Immune Defic Syndr. 2012;62(5):534-539. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23187949.
41. Atrio J, Stanczyk FZ, Neely M, Cherala G, Kovacs A, Mishell DR, Jr. Effect of protease inhibitors on steady-state pharmacokinetics of oral norethindrone contraception in HIV-infected women. J Acquir Immune Defic Syndr. 2014;65(1):72-77. Available at: http://www.ncbi.nlm.nih.gov/pubmed/24025339.
42. Crauwels HM, van Heeswijk RP, Buelens A, Stevens M, Hoetelmans RM. Lack of an effect of rilpivirine on the pharmacokinetics of ethinylestradiol and norethindrone in healthy volunteers. Int J Clin Pharmacol Ther. 2014;52(2):118-128. Available at: http://www.ncbi.nlm.nih.gov/pubmed/24161160.
43. Landolt NK, Phanuphak N, Ubolyam S, et al. Significant decrease of ethinylestradiol with nevirapine, and of etonogestrel with efavirenz in HIV-positive women. J Acquir Immune Defic Syndr. 2014;66(2):e50-52. Available at: http://www.ncbi.nlm.nih.gov/pubmed/24608892.
44. Perry SH, Swamy P, Preidis GA, Mwanyumba A, Motsa N, Sarero HN. Implementing the jadelle implant for women living with HIV in a resource-limited setting in sub-Saharan Africa: concerns for drug interactions leading to unintended pregnancies. AIDS. 2014;28(5). Available at: http://www.ncbi.nlm.nih.gov/pubmed/24401645.
45. Thurman AR, Anderson S, Doncel GF. Effects of hormonal contraception on antiretroviral drug metabolism, pharmacokinetics and pharmacodynamics. Am J Reprod Immunol. 2014;71(6):523-530. Available at: http://www.ncbi.nlm.nih.gov/pubmed/24521428.
46. Luque AE, Cohn SE, Park JG, et al. Depot medroxyprogesterone acetate in combination with a twice-daily lopinavir-ritonavir-based regimen in HIV-infected women showed effective contraception and a lack of clinically significant interactions, with good safety and tolerability: results of the ACTG 5283 study. Antimicrob Agents Chemother. 2015;59(4):2094-2101. Available at: http://www.ncbi.nlm.nih.gov/pubmed/25624326.
47. Song IH, Borland J, Chen S, Wajima T, Peppercorn AF, Piscitelli SC. Dolutegravir has no effect on the pharmacokinetics of oral contraceptives with norgestimate and ethinyl estradiol. Ann Pharmacother. 2015;49(7):784-789. Available at: http://www.ncbi.nlm.nih.gov/pubmed/25862012.
48. Scarsi KK, Darin KM, Nakalema S, et al. Unintended pregnancies observed with combined use of the levonorgestrel contraceptive implant and efavirenz-based antiretroviral therapy: a three-Arm pharmacokinetic evaluation over 48 weeks. Clin Infect Dis. 2016;62(6):675-682. Available at: http://www.ncbi.nlm.nih.gov/pubmed/26646680.
49. Nanda K, Stuart GS, Robinson J, Gray AL, Tepper NK, Gaffield ME. Drug interactions between hormonal contraceptives and antiretrovirals. AIDS. 2017;31(7):917-952. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28060009.
50. Elliot ER, Bisdomini E, Penchala SD, Khoo S, Nwokolo N, Boffito M. Pharmacokinetics (PK) of ethinylestradiol/levonorgestrel co-administered with atazanavir/cobicistat. HIV Res Clin Pract. 2019:1-10. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31335301.
51. Majeed SR, West S, Ling KH, Das M, Kearney BP. Confirmation of the drug-drug interaction potential between cobicistat-boosted antiretroviral regimens and hormonal contraceptives. Antivir Ther. 2020;24(8):557-566. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31933482.
52. Neary M, Chappell CA, Scarsi KK, et al. Effect of patient genetics on etonogestrel pharmacokinetics when combined with efavirenz or nevirapine ART. J Antimicrob Chemother. 2019;74(10):3003-3010. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31299074.
53. Patel RC, Stalter RM, Thomas KK, et al. A pharmacokinetic and pharmacogenetic evaluation of contraceptive implants and antiretroviral therapy among women in Kenya and Uganda. AIDS. 2019;33(13):1995-2004. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31306173.
54. Scarsi KK, Cramer YS, Rosenkranz SL, et al. Antiretroviral therapy and vaginally administered contraceptive hormones: a three-arm, pharmacokinetic study. Lancet HIV. 2019;6(9):e601-e612. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31498109.
55. Sekar VJ, Lefebvre E, Guzman SS, et al. Pharmacokinetic interaction between ethinyl estradiol, norethindrone and darunavir with low-dose ritonavir in healthy women. Antivir Ther. 2008;13(4):563-569. Available at: https://www.ncbi.nlm.nih.gov/pubmed/18672535.
56. Weinberg A, Park JG, Bosch R, et al. Effect of depot medoxyprogesterone acetate on immune functions and inflammatory markers of HIV-infected women. J Acquir Immune Defic Syndr. 2016;71(2):137-145. Available at: http://www.ncbi.nlm.nih.gov/pubmed/26413850.
57. Leticee N, Viard JP, Yamgnane A, Karmochkine M, Benachi A. Contraceptive failure of etonogestrel implant in patients treated with antiretrovirals including efavirenz. Contraception. 2012;85(4):425-427. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22036046.
58. Patel RC, Onono M, Gandhi M, et al. Pregnancy rates in HIV-positive women using contraceptives and efavirenz-based or nevirapine-based antiretroviral therapy in Kenya: a retrospective cohort study. Lancet HIV. 2015;2(11):e474-482. Available at: http://www.ncbi.nlm.nih.gov/pubmed/26520927.
59. Chappell CA, Lamorde M, Nakalema S, et al. Efavirenz decreases etonogestrel exposure: a pharmacokinetic evaluation of implantable contraception with antiretroviral therapy. AIDS. 2017;31(14):1965-1972. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28692531.
60. Pyra M, Heffron R, Mugo NR, et al. Effectiveness of hormonal contraception in HIV-infected women using antiretroviral therapy. AIDS. 2015;29(17):2353-2359. Available at: http://www.ncbi.nlm.nih.gov/pubmed/26544706.
61. Pfitzer A, Wille J, Wambua J, et al. Contraceptive implant failures among women using antiretroviral therapy in western Kenya: a retrospective cohort study. Gates Open Res. 2019;3:1482. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32051928.
62. Tang JH, Davis NL, Corbett AH, et al. Effect of efavirenz on levonorgestrel concentrations among Malawian levonorgestrel implant users for up to 30 months of concomitant use: a subanalysis of a randomized clinical trial. Contracept X. 2020;2:100027. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33364598.
63. Haas DW, Cramer YS, Godfrey C, et al. Pharmacogenetic interactions between antiretroviral drugs and vaginally administered hormonal contraceptives. Pharmacogenet Genomics. 2020;30(3):45-53. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32106141.
64. Mngqibisa R, Kendall MA, Dooley K, et al. Pharmacokinetics and pharmacodynamics of depot medroxyprogesterone acetate in African women receiving treatment for human immunodeficiency virus and tuberculosis: potential concern for standard dosing frequency. Clin Infect Dis. 2020;71(3):517-524. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31504342.
65. Francis J, Mngqibisa R, McIlleron H, et al. A semimechanistic pharmacokinetic model for depot medroxyprogesterone acetate and drug-drug interactions with antiretroviral and antituberculosis treatment. Clin Pharmacol Ther. 2021;110(4):1057-1065. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34151439.
66. Haas DW, Mngqibisa R, Francis J, et al. Pharmacogenetics of interaction between depot medroxyprogesterone acetate and efavirenz, rifampicin, and isoniazid during treatment of HIV and tuberculosis. Pharmacogenet Genomics. 2022;32(1):24-30. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34369424.
67. Blair CS, Li S, Chau G, et al. Brief report: hormonal contraception use and cabotegravir pharmacokinetics in HIV-uninfected women enrolled in HPTN 077. J Acquir Immune Defic Syndr. 2020;85(1):93-97. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32452972.
68. Tepper NK, Curtis KM, Cox S, Whiteman MK. Update to U.S. medical eligibility criteria for contraceptive use, 2016: updated recommendations for the use of contraception among women at high risk for HIV infection. MMWR Morb Mortal Wkly Rep. 2020;69(14):405-410. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32271729.
69. Bishop IJ, Gertz AM, Simon B, et al. Etonogestrel concentrations among contraceptive implant users in Botswana using and not using dolutegravir-based antiretroviral therapy. Contraception. 2020;102(3):174-179. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32387328.
70. Vieira CS, Bahamondes MV, de Souza RM, et al. Effect of antiretroviral therapy including lopinavir/ritonavir or efavirenz on etonogestrel-releasing implant pharmacokinetics in HIV-positive women. J Acquir Immune Defic Syndr. 2014;66(4):378-385. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24798768.
71. Polis CB, Curtis KM. Use of hormonal contraceptives and HIV acquisition in women: a systematic review of the epidemiological evidence. Lancet Infect Dis. 2013;13(9):797-808. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23871397.
72. Watts DH, Park JG, Cohn SE, et al. Safety and tolerability of depot medroxyprogesterone acetate among HIV-infected women on antiretroviral therapy: ACTG A5093. Contraception. 2008;77(2):84-90. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18226670.
73. Clark RA, Theall K. Population-based study evaluating association between selected antiretroviral therapies and potential oral contraceptive failure. J Acquir Immune Defic Syndr. 2004;37(1):1219-1220. Available at: https://ncbi.nlm.nih.gov/pubmed/15319685.
74. Landolt NK, Phanuphak N, Ubolyam S, et al. Efavirenz, in contrast to nevirapine, is associated with unfavorable progesterone and antiretroviral levels when coadministered with combined oral contraceptives. J Acquir Immune Defic Syndr. 2013;62(5):534-539. Available at: https://ncbi.nlm.nih.gov/pubmed/23187949.
75. Scholler-Gyure M, Kakuda TN, Woodfall B, et al. Effect of steady-state etravirine on the pharmacokinetics and pharmacodynamics of ethinylestradiol and norethindrone. Contraception. 2009;80(1):44-52. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19501215.
76. Mildvan D, Yarrish R, Marshak A, et al. Pharmacokinetic interaction between nevirapine and ethinyl estradiol/norethindrone when administered concurrently to HIV-infected women. J Acquir Immune Defic Syndr. 2002;29(5):471-477. Available at: https://ncbi.nlm.nih.gov/pubmed/11981363.
77. Stuart GS, Moses A, Corbett A, et al. Combined oral contraceptives and antiretroviral PK/PD in Malawian women: pharmacokinetics and pharmacodynamics of a combined oral contraceptive and a generic combined formulation antiretroviral in Malawi. J Acquir Immune Defic Syndr. 2011;58(2):e40-43. Available at: https://ncbi.nlm.nih.gov/pubmed/21921726.
78. Muro E, Droste JA, Hofstede HT, Bosch M, Dolmans W, Burger DM. Nevirapine plasma concentrations are still detectable after more than 2 weeks in the majority of women receiving single-dose nevirapine: implications for intervention studies. J Acquir Immune Defic Syndr. 2005;39(4):419-421. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16010163.
79. Day S, Graham SM, Masese LN, et al. A prospective cohort study of the effect of depot medroxyprogesterone acetate on detection of plasma and cervical HIV-1 in women initiating and continuing antiretroviral therapy. J Acquir Immune Defic Syndr. 2014;66(4):452-456. Available at: https://ncbi.nlm.nih.gov/pubmed/24798764.
80. Hubacher D, Liku J, Kiarie J, et al. Effect of concurrent use of anti-retroviral therapy and levonorgestrel sub-dermal implant for contraception on CD4 counts: a prospective cohort study in Kenya. J Int AIDS Soc. 2013;16:18448. Available at: https://ncbi.nlm.nih.gov/pubmed/23458102.
81. Myer L, Carter RJ, Katyal M, Toro P, El-Sadr WM, Abrams EJ. Impact of antiretroviral therapy on incidence of pregnancy among HIV-infected women in Sub-Saharan Africa: a cohort study. PLoS Med. 2010;7(2):e1000229. Available at: https://ncbi.nlm.nih.gov/pubmed/20161723.
82. Nanda K, Delany-Moretlwe S, Dube K, et al. Nevirapine-based antiretroviral therapy does not reduce oral contraceptive effectiveness. AIDS. 2013;27 Suppl 1:S17-25. Available at: https://ncbi.nlm.nih.gov/pubmed/24088680.
83. Khalilieh SG, Yee KL, Sanchez RI, et al. Doravirine and the potential for CYP3A-mediated drug-drug interactions. Antimicrob Agents Chemother. 2019;63(5):e02016-02018. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30783000.
84. Zhang J, Chung E, Yones C, et al. The effect of atazanavir/ritonavir on the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and norgestimate in healthy women. Antivir Ther. 2011;16(2):157-164. Available at: https://ncbi.nlm.nih.gov/pubmed/21447864.
85. DuBois BN, Atrio J, Stanczyk FZ, Cherala G. Increased exposure of norethindrone in HIV+ women treated with ritonavir-boosted atazanavir therapy. Contraception. 2015;91(1):71-75. Available at: https://ncbi.nlm.nih.gov/pubmed/25245190.
86. Atazanavir (Reyataz) [package insert]. Food and Drug Administration. 2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021567s044,206352s008lbl.pdf.
87. Abel S, Russell D, Whitlock LA, Ridgway CE, Muirhead GJ. Effect of maraviroc on the pharmacokinetics of midazolam, lamivudine/zidovudine, and ethinyloestradiol/levonorgestrel in healthy volunteers. Br J Clin Pharmacol. 2008;65 Suppl 1:19-26. Available at: https://ncbi.nlm.nih.gov/pubmed/18333862.
88. Stribild (elvitegravir, cobicitstat, emtricitabine, tenofovir disaproxil fumarate) [package insert]. Food and Drug Administration. 2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/203100s035lbl.pdf.
89. Genvoya (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide) [package insert]. Food and Drug Administration. 2021. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/207561s025lbl.pdf.
90. Anderson MS, Hanley WD, Moreau AR, et al. Effect of raltegravir on estradiol and norgestimate plasma pharmacokinetics following oral contraceptive administration in healthy women. Br J Clin Pharmacol. 2011;71(4):616-620. Available at: https://ncbi.nlm.nih.gov/pubmed/21395656.